Genotype-covariate interaction effects and the heritability of adult body mass index

被引：105

作者：

Robinson, Matthew R. ^{[1
,2
]}

English, Geoffrey ^{[1
]}

Moser, Gerhard ^{[1
]}

Lloyd-Jones, Luke R. ^{[1
]}

Triplett, Marcus A. ^{[3
]}

Zhu, Zhihong ^{[1
]}

Nolte, Ilja M. ^{[4
]}

van Vliet-Ostaptchouk, Jana V. ^{[4
,5
]}

Snieder, Harold ^{[4
]}

Esko, Tonu ^{[6
,7
,8
,9
]}

Milani, Lili ^{[6
]}

Magi, Reedik ^{[6
]}

Metspalu, Andres ^{[6
,10
]}

Magnusson, Patrik K. E. ^{[11
]}

Pedersen, Nancy L. ^{[11
]}

Ingelsson, Erik ^{[12
,13
]}

Johannesson, Magnus ^{[14
]}

Yang, Jian ^{[1
]}

Cesarini, David ^{[15
]}

Visscher, Peter M. ^{[1
]}

机构：

[1] Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia

[2] Univ Lausanne, Dept Computat Biol, Lausanne, Switzerland

[3] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia

[4] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands

[5] Univ Groningen, Univ Med Ctr Groningen, Dept Endocrinol, Groningen, Netherlands

[6] Univ Tartu, Estonia Genome Ctr, Tartu, Estonia

[7] Boston Childrens Hosp, Div Endocrinol, Cambridge, MA USA

[8] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA

[9] Harvard Med Sch, Dept Genet, Boston, MA USA

[10] Univ Tartu, Inst Mol & Cell Biol, Tartu, Estonia

[11] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden

[12] Uppsala Univ, Dept Med Sci, Mol Epidemiol & Sci Life Lab, Uppsala, Sweden

[13] Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA

[14] Stockholm Sch Econ, Stockholm, Sweden

[15] NYU, Dept Econ, Ctr Expt Social Sci, 550 1St Ave, New York, NY 10003 USA

来源：

NATURE GENETICS | 2017年 / 49卷 / 08期

基金：

美国国家卫生研究院; 瑞典研究理事会; 澳大利亚研究理事会; 英国医学研究理事会;

关键词：

GENETIC ARCHITECTURE; MISSING HERITABILITY; SEX-DIFFERENCES; FTO GENOTYPE; HUMAN HEIGHT; TRAITS; VARIANTS; TWIN; ASSOCIATION; VARIABILITY;

D O I：

10.1038/ng.3912

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Obesity is a worldwide epidemic, with major health and economic costs. Here we estimate heritability for body mass index (BMI) in 172,000 sibling pairs and 150,832 unrelated individuals and explore the contribution of genotype-covariate interaction effects at common SNP loci. We find evidence for genotype-age interaction (likelihood ratio test (LRT) = 73.58, degrees of freedom (df) = 1, P = 4.83 x 10(-18)), which contributed 8.1% (1.4% s.e.) to BMI variation. Across eight self-reported lifestyle factors, including diet and exercise, we find genotype-environment interaction only for smoking behavior (LRT = 19.70, P = 5.03 x 10(-5) and LRT = 30.80, P = 1.42 x 10(-8)), which contributed 4.0% (0.8% s.e.) to BMI variation. Bayesian association analysis suggests that BMI is highly polygenic, with 75% of the SNP heritability attributable to loci that each explain <0.01% of the phenotypic variance. Our findings imply that substantially larger sample sizes across ages and lifestyles are required to understand the full genetic architecture of BMI.

引用

页码：1174 / +

页数：12

共 55 条

[1]

Björklund A, 2005, UNEQUAL CHANCES: FAMILY BACKGROUND AND ECONOMIC SUCCESS, P145

[2] Genetics of Obesity: What have we Learned? [J].

Choquet, Helene ;

Meyre, David .

CURRENT GENOMICS, 2011, 12 (03) :169-179

[3] Genetic variability of adult body mass index: A longitudinal assessment in Framingham families [J].

Coady, SA ;

Jaquish, CE ;

Fabsitz, RR ;

Larson, MG ;

Cupples, LA ;

Myers, RH .

OBESITY RESEARCH, 2002, 10 (07) :675-681

[4]

Elks Cathy E, 2012, Front Endocrinol (Lausanne), V3, P29, DOI 10.3389/fendo.2012.00029

[5] Improving accuracy of genomic predictions within and between dairy cattle breeds with imputed high-density single nucleotide polymorphism panels [J].

Erbe, M. ;

Hayes, B. J. ;

Matukumalli, L. K. ;

Goswami, S. ;

Bowman, P. J. ;

Reich, C. M. ;

Mason, B. A. ;

Goddard, M. E. .

JOURNAL OF DAIRY SCIENCE, 2012, 95 (07) :4114-4129

[6] Computing approximate standard errors for genetic parameters derived from random regression models fitted by average information REML [J].

Fischer, TM ;

Gilmour, AR ;

van der Werf, JHJ .

GENETICS SELECTION EVOLUTION, 2004, 36 (03) :363-369

[7] Warped linear mixed models for the genetic analysis of transformed phenotypes [J].

Fusi, Nicolo ;

Lippert, Christoph ;

Lawrence, Neil D. ;

Stegle, Oliver .

NATURE COMMUNICATIONS, 2014, 5

[8] Genomic selection: prediction of accuracy and maximisation of long term response [J].

Goddard, Mike .

GENETICA, 2009, 136 (02) :245-257

[9] Stable Genes and Changing Environments: Body Mass Index Across Adolescence and Young Adulthood [J].

Haberstick, Brett C. ;

Lessem, Jeffery M. ;

McQueen, Matthew B. ;

Boardman, Jason D. ;

Hopfer, Christian J. ;

Smolen, Andrew ;

Hewitt, John K. .

BEHAVIOR GENETICS, 2010, 40 (04) :495-504

[10] Inference of the Genetic Architecture Underlying BMI and Height with the Use of 20,240 Sibling Pairs [J].

Hemani, Gibran ;

Yang, Jian ;

Vinkhuyzen, Anna ;

Powell, Joseph E. ;

Willemsen, Gonneke ;

Hottenga, Jouke-Jan ;

Abdellaoui, Abdel ;

Mangino, Massimo ;

Valdes, Ana M. ;

Medland, Sarah E. ;

Madden, Pamela A. ;

Heath, Andrew C. ;

Henders, Anjali K. ;

Nyholt, Dale R. ;

de Geus, Eco J. C. ;

Magnusson, Patrik K. E. ;

Ingelsson, Erik ;

Montgomery, Grant W. ;

Spector, Timothy D. ;

Boomsma, Dorret I. ;

Pedersen, Nancy L. ;

Martin, Nicholas G. ;

Visscher, Peter M. .

AMERICAN JOURNAL OF HUMAN GENETICS, 2013, 93 (05) :865-875

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